Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson's Disease Patients

Abstract

In Parkinson's Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based on a chronic-oxidative stress situation, is involved in the rate of aging. We analyzed several functions in isolated peripheral blood neutrophils and mononuclear cells from PD stage 2 patients, and compared the results to those in healthy elderly and adult controls. Several oxidative stress and damage parameters were studied in whole blood cells. The results showed an impairment of the lymphoproliferative response in stimulated conditions in the PD patients compared with age-matched controls, who also showed typical immunosenescence in comparison with adult individuals. Higher oxidative stress and damage were observed in whole blood cells from PD patients (lower glutathione peroxidase activity, and higher oxidized glutathione and malondialdehyde contents). Our results suggest an accelerated immunosenescence in PD stage 2, and that several of the parameters studied could be appropriate peripheral biomarkers in the early stages of PD.

Keywords: Parkinson’s Disease; biomarkers; blood cells; immune functions; immunosenescence; lymphoproliferation; oxidative damage; oxidative stress.

Figure 1

Immune function parameters in isolated peripheral blood neutrophils and mononuclear cells of Parkinson´s Disease (PD) stage 2 patients, and adult and elderly healthy controls. Chemotaxis index (C.I.) of (A) neutrophils and (B) lymphocytes; (C) phagocytic index (P.I.) and (D) phagocytic efficiency (%) of neutrophils and (E) natural killer (NK) cytotoxic activity (% lysis). Data are shown as the mean (horizontal bar) of 18–45 values corresponding to the numbers of subjects analyzed in each group (20 adults, 34 elderly, and 45 PD). Each point represents the mean of duplicate assays. The green points represent the values in five PD patients treated with levodopa. a: p < 0.05, aa: p < 0.01, and aaa: p < 0.001 with respect to the value in adult subjects.

Figure 2

Stimulation of proliferation in response to phytohemagglutinin (PHA) and lipopolysaccharide (LPS) (1 μg/mL) in isolated peripheral blood mononuclear cells of Parkinson´s Disease (PD) stage 2 patients, as well as of adult and elderly healthy controls. Lymphoproliferation (48 h incubation) in counts per minute (c.p.m.) with the mitogens (A) PHA and (B) LPS. Lymphoproliferation capacity (%) in response to (C) PHA and (D) LPS providing 100% to the c.p.m. in basal conditions. Data are shown as the mean (horizontal bar) of 16–45 values corresponding to the number of subjects analyzed in each group (20 adults, 34 elderly, and 45 PD). Each point represents the mean of duplicate assays. The green points represent the values in five PD patients treated with levodopa. aaa: p < 0.001 with respect to the value in adult subjects; * p < 0.05 and *** p < 0.001 with respect to the value in elderly subjects.

Figure 3

Oxidative stress and lipid peroxidation parameters in whole blood cells, containing both total red blood cells and leukocyte populations, of Parkinson´s Disease (PD) stage 2 patients, as well as of adult and elderly healthy subjects. (A) Glutathione peroxidase (GPx) and (B) glutathione reductase (GR) activities (U/mg protein); (C) intracellular reduced glutathione (GSH) concentrations and (D) oxidized glutathione (GSSG) contents (nmol/mg protein); (E) GSSG/GSH ratios; and (F) intracellular malondialdehyde (MDA) contents (nmol/mg protein). Data are shown as the mean (horizontal bar) of 16–23 values corresponding to the number of subjects analyzed in each group (20 adult, 23 elderly, 26 PD). Each value is the mean of duplicate assays. The green points represent the values in five PD patients treated with levodopa. a: p < 0.05, aa: p < 0.01, and aaa: p < 0.001 with respect to the value in adult subjects; * p < 0.05, ** p < 0.01, and *** p < 0.001 with respect to the value in elderly subjects.